In rodents, FcepsilonRI has only been detected so far on the surface of mast cells, basophils, and non-B non-T cells. The role played by this receptor in initiating cell degranulation and the release of the mediators of allergic reactions is clearly established. In humans however, the cell distribution of Fc(epsilon)RI appears to be different. We found last year that human Langerhans cells from the skin of normal individuals also express Fc(epsilon)RI. More recently, we also found that dermal dendritic cells express Fc(epsilon)RI as well. In addition, monocytes of allergic individuals also express this receptor. We are attempting to define the factors which regulate expression of Fc(epsilon)RI on these cells and the role of this receptor in this new context. As a way to further our understanding of these questions, we are also generating transgenic mice overexpressing human alpha chains under the control of the human promotor.